Aggressive fluid strategy didn't avert progression to severe pancreatitis
The randomized trial was stopped early due to lack of benefit and significantly higher risk of fluid overload in patients receiving an aggressive fluid resuscitation strategy compared to those getting moderate resuscitation.
Aggressive fluid resuscitation did not improve outcomes in patients with acute pancreatitis, a trial found.
Researchers conducted the study at 18 centers in India, Italy, Mexico, and Spain and randomized patients with acute pancreatitis to receive either aggressive or moderate resuscitation with lactated Ringer's solution. The aggressive strategy involved a bolus of 20 mL/kg, followed by 3 mL/kg/h, whereas the moderate strategy gave a bolus of 10 mL/kg to patients with hypovolemia and no bolus to patients with normovolemia, followed by 1.5 mL/kg/h. The researchers assessed patients at 12, 24, 48, and 72 hours, with fluid resuscitation adjusted according to clinical status. Results were published by the New England Journal of Medicine on Sept. 15.
The trial's data and safety monitoring board stopped the study after its first interim analysis, when 248 of a planned 744 patients had been enrolled, because the interim data showed a difference between groups in the study's safety outcome but no difference in the primary outcome, development of moderately severe or severe pancreatitis during hospitalization (22.1% with aggressive therapy vs. 17.3% with moderate therapy; adjusted relative risk [RR], 1.30 [95% CI, 0.78 to 2.18]; P=0.32). The primary safety outcome of fluid overload developed in 20.5% and 6.3%, respectively (adjusted RR, 2.85 [95% CI, 1.36 to 5.94]; P=0.004). The median duration of hospitalization was six days in the aggressive group and five days in the moderate group.
“These findings do not support current management guidelines, which recommend early aggressive resuscitation for the treatment of acute pancreatitis,” said the study authors. “The absence of an efficacy signal for aggressive hydration is of practical importance given that it challenges a strong predilection in many clinicians for the use of early high-volume hydration.”
Since the study was terminated early, it was underpowered on the primary outcome; however, the data and safety monitoring board was concerned at the interim analysis that a much larger sample size would be needed to show superiority in either group, which would expose many patients to risk of fluid overload, the study authors said. Another limitation is that the trial was open label. “It is possible that hydration in the aggressive-resuscitation group may have been too aggressive, and future trials exploring more restrictive strategies should be encouraged,” the authors noted.
The trial results definitively answer the question of how much lactated Ringer's solution is too much, according to an accompanying editorial. “These results are stunning and, given the carefully crafted trial methods, irrefutable,” the editorialist wrote.
Clinicians can draw several conclusions from this trial, he noted. “First, clinicians should focus on a steady rate of initial resuscitation—no more than 1.5 ml per kilogram of body weight per hour—and should administer a bolus of 10 ml per kilogram only if there are signs of initial hypovolemia. Second, careful clinical and hemodynamic monitoring are essential during the first 72 hours after admission to make sure that patients remain euvolemic and to avoid fluid overload. Third, diuresis in patients with fluid overload in the first 72 hours is most likely beneficial and certainly not detrimental to important clinical outcomes,” the editorial said.